Stewart D J, Leventer S M, Hanin I, Vanderwolf C H
Pharmacol Biochem Behav. 1987 Feb;26(2):357-64. doi: 10.1016/0091-3057(87)90130-4.
The effects of intracerebroventricular (ICV) injections of ethylcholine aziridinium ion (AF64A; 3 nmol/3 microliters/side) on the pattern of hippocampal electrical activity were studied in freely moving and urethane anesthetized rats. AF64A treated rats showed a significantly smaller increase in 6-12 Hz hippocampal rhythmical slow activity (RSA) with struggling in the no drug condition in comparison to the vehicle injected rats. However, neither AF64A treatment nor a control injection abolished the presumed cholinergic form of RSA that is present during urethane anesthesia. Systemic injection of atropine in waking rats did not significantly alter RSA in either the AF64A or vehicle injected rats. Analysis of histological brain sections revealed extensive damage to the fimbria-fornix, CA3 of the hippocampus, corpus callosum, neocortex and striatum. Acetylcholinesterase staining of the remaining hippocampus appeared normal in the AF64a treated rats. The data indicate that the depletion of cholinergic markers in the hippocampus following ICV administration of AF64A is not sufficient to disrupt the cholinergic form of RSA. Further, the question is discussed as to whether AF64A produces its cholinoselective effects via a specific pharmacological action or through a nonspecific destruction of the fimbria-fornix.
在自由活动和经乌拉坦麻醉的大鼠中,研究了脑室内注射氮丙啶乙基胆碱离子(AF64A;3纳摩尔/3微升/侧)对海马电活动模式的影响。与注射溶剂的大鼠相比,在无药物状态下挣扎时,接受AF64A治疗的大鼠海马6 - 12赫兹节律性慢活动(RSA)的增加显著较小。然而,AF64A治疗和对照注射均未消除在乌拉坦麻醉期间存在的假定胆碱能形式的RSA。在清醒大鼠中全身注射阿托品,对接受AF64A或注射溶剂的大鼠的RSA均无显著影响。对脑组织切片的组织学分析显示,穹窿 - 海马伞、海马CA3区、胼胝体、新皮层和纹状体有广泛损伤。在接受AF64A治疗的大鼠中,剩余海马的乙酰胆碱酯酶染色看起来正常。数据表明,脑室内给予AF64A后海马中胆碱能标记物的耗竭不足以破坏胆碱能形式的RSA。此外,还讨论了AF64A是通过特定的药理作用还是通过对穹窿 - 海马伞的非特异性破坏产生其胆碱选择性作用的问题。